Familial hypomagnesemia with hypercalciuria and nephrocalcinosis (FHNNC) is a rare autosomal recessive renal tubulopathy disorder characterized by excessive urinary loss of calcium and magnesium, polyuria, polydipsia, bilateral nephrocalcinosis, progressive chronic kidney disease, and renal failure. Also, sometimes amelogenesis imperfecta and severe ocular abnormalities are involved. The CLDN-16 and CLDN-19 genes encode the tight junction proteins claudin-16 and claudin-19, respectively, in the thick ascending loop of Henle in the kidney, epithelial cells of the retina, dental enamel, etc. Loss of function of the CLDN-16 and/or CLDN-19 genes leads to FHHNC. We present a case of FHHNC type 1, which was first confused with autosomal dominant hypocalcaemia (ADH) due to the presence of a very low serum parathyroid hormone (PTH) concentration and other similar clinical features before the genetic investigations. After the exome sequencing, FHHNC type 1 was confirmed by uncovering a novel homozygous missense mutation in the CLDN-16 gene (Exon 2, c.374 T > C) which causes, altered protein structure with F55S. Associated clinical, biochemical, and imaging findings also corroborate final diagnosis. Our findings expand the spectrum of the CLDN-16 mutation, which will further help in the genetic diagnosis and management of FHNNC.

家族性低镁血症伴高钙尿症和肾钙质沉着症 (FHNNC) 是一种罕见的常染色体隐性肾小管病，其特征是尿中钙和镁流失过多、多尿、多饮、双侧肾钙质沉着症、进行性慢性肾病和肾功能衰竭。此外，有时还涉及釉质生成不全和严重的眼部异常。CLDN -16 和CLDN-19基因分别编码紧密连接蛋白claudin-16和claudin-19，存在于肾脏的厚升环Henle、视网膜上皮细胞、牙釉质等。 CLDN -16和/或CLDN-19基因导致 FHHNC。我们介绍了一例 FHHNC 1 型病例，由于在基因研究之前存在极低的血清甲状旁腺激素 (PTH) 浓度和其他类似的临床特征，该病例首次与常染色体显性低钙血症 (ADH) 相混淆。外显子组测序后，通过发现CLDN-16基因（外显子 2，c.374 T > C）中的新型纯合错义突变，确认了 FHHNC 1 型，该突变导致 F55S 的蛋白质结构发生改变。相关的临床、生化和影像学检查结果也证实了最终诊断。我们的研究结果扩大了CLDN-16突变谱，这将进一步有助于 FHNNC 的基因诊断和管理。